Effects of anti-inflammatory vagus nerve stimulation in endotoxemic rats on blood and spleen lymphocyte subsets

Effects of anti-inflammatory vagus nerve stimulation in endotoxemic rats on blood and spleen lymphocyte subsets

S. Mihaylova, H. Schweighöfer, H. Hackstein, B. Rosengarten 

Background: Anti-inflammatory cytokine effects of vagus nerve stimulation in sepsis syndromes are well established. Effects on immune cells are less clear. Therefore, we studied changes in peripheral and spleen leukocyte subsets in an endotoxic rat sepsis model.

Methods: Ventilated and sedated adult male SD rats received 5 mg/kg b.w. lipopolysaccharide intravenously to induce endotoxic sepsis. Controls and a group with both-sided vagotomy were compared to animals with both sided vagotomy and left distal vagus nerve stimulation. 4.5 h after sepsis induction immune cell counts and types in the peripheral blood and spleen were determined [T-lymphocytes (CD3+), T-helper cells (CD3+ CD4+), activated T-helper cells (CD3+ CD4+ CD134+), cytotoxic T-cells (CD3+ CD8+), activated cytotoxic T-cells (CD3+ CD8+ CD134+), B-lymphocytes (CD45R+ CD11cneg-dim), dendritic cells (CD11c+ OX-62 +), natural killer cells (CD161+ CD3neg) and granulocytes (His48 +)] together with cytokine and chemokine plasma levels (IL10; IFN-g, TNF-a, Cxcl5, Ccl5).

Results: Blood cell counts declined in all LPS groups. However, vagus nerve stimulation but not vagotomy activated cytotoxic T-cells. Vagotomy also depleted natural killer cells. In the spleen, vagotomy resulted in a strong decline of all cell types which was not present in the other septic groups where only granulocyte numbers declined.

Conclusion: Vagotomy strongly declines immune cell counts in the septic spleen. This could not be explained by an evasion or apoptosis of cells. A marginalisation of spleen immune cells into the peripheral microcirculation might be therefore most likely. Further studies are warranted to clear this issue.